CIRCUIT-LEVEL MAPPING OF LOCOMOTOR NETWORK RECRUITMENT DURING NEUROMODULATORY STIMULATION AFTER SPINAL CORD INJURY

Spinal cord injury (SCI) often results in locomotor impairments, yet substantial supraspinal pathways can remain structurally intact, representing promising targets for functional recovery. Midbrain locomotor regions, including the cuneiform nucleus (CnF), are increasingly explored as entry points to engage residual descending control and enhance rehabilitation outcomes. However, despite extensive work dissecting individual components of supraspinal and spinal locomotor control, it remains largely undefined how these circuits are integratively recruited across levels during locomotion, and how this distributed recruitment is reconfigured after SCI and neuromodulation. Here, we used activity-dependent genetic labeling in TRAP2 mice combined with quantitative locomotor profiling to map locomotion-related networks across defined behavioral conditions. Neurons were permanently tagged during periods of no movement, walking alone, or walking coupled with optical stimulation of the CnF, allowing discrimination between locomotor recruitment from stimulation-enhanced recruitment. Using this framework in intact and thoracic incomplete SCI mice, we mapped distributed activity-defined neuronal populations across supraspinal nuclei and spinal cord regions during locomotion and neuromodulatory stimulation. Together, this work establishes a circuit-level anatomical framework that enables future causal and mechanistic interrogation of activity-defined locomotor circuits, providing a foundation for mechanism-guided neuromodulatory rehabilitation strategies after SCI.